Shen Hanchen, Ding Lili, Baig Mehdi, Tian Jingyan, Wang Yang, Huang Wendong
School of Pharmacy, Fudan University, Shanghai 201203, China.
Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Cell Stress. 2021 Jan 5;5(1):1-18. doi: 10.15698/cst2021.01.239.
Bariatric surgery is one of the most effective treatment options for severe obesity and its comorbidities. However, it is a major surgery that poses several side effects and risks which impede its clinical use. Therefore, it is urgent to develop alternative safer pharmacological approaches to mimic bariatric surgery. Recent studies suggest that bile acids are key players in mediating the metabolic benefits of bariatric surgery. Bile acids can function as signaling molecules by targeting bile acid nuclear receptors and membrane receptors, like FXR and TGR5 respectively. In addition, the composition of bile acids is regulated by either the hepatic sterol enzymes such as CYP8B1 or the gut microbiome. These bile acid related targets all play important roles in regulating metabolism. Drug development based on these targets could provide new hope for patients without the risks of surgery and at a lower cost. In this review, we summarize the most updated progress on bile acid related targets and development of small molecules as drug candidates based on these targets.
减肥手术是治疗重度肥胖及其合并症最有效的方法之一。然而，这是一项大手术，会带来多种副作用和风险，阻碍了其临床应用。因此，迫切需要开发更安全的替代药物方法来模拟减肥手术。最近的研究表明，胆汁酸是介导减肥手术代谢益处的关键因素。胆汁酸可分别通过靶向胆汁酸核受体和膜受体（如FXR和TGR5）发挥信号分子的作用。此外，胆汁酸的组成受肝脏固醇酶（如CYP8B1）或肠道微生物群的调节。这些与胆汁酸相关的靶点在调节新陈代谢中都起着重要作用。基于这些靶点的药物开发可以为患者带来新的希望，避免手术风险，且成本更低。在本综述中，我们总结了胆汁酸相关靶点的最新进展以及基于这些靶点开发小分子作为候选药物的情况。
